Daily Cardiology Research Analysis
A multicountry RCT in Africa showed that starting low-dose dual antihypertensive therapy is noninferior to stepped monotherapy, informing first-line hypertension management. A mechanistic study identified PP2A activation as a promising therapeutic strategy to prevent thoracic aortic aneurysm progression in Marfan syndrome by suppressing mTOR signaling. A large cluster randomized crossover trial found that restricting intraoperative benzodiazepines during cardiac surgery did not significantly red
Summary
A multicountry RCT in Africa showed that starting low-dose dual antihypertensive therapy is noninferior to stepped monotherapy, informing first-line hypertension management. A mechanistic study identified PP2A activation as a promising therapeutic strategy to prevent thoracic aortic aneurysm progression in Marfan syndrome by suppressing mTOR signaling. A large cluster randomized crossover trial found that restricting intraoperative benzodiazepines during cardiac surgery did not significantly reduce postoperative delirium.
Research Themes
- Hypertension treatment strategies and global health
- Translational mechanisms in aortopathy (PP2A–mTOR axis)
- Perioperative neurocognitive outcomes in cardiac surgery
Selected Articles
1. Treatment Strategies to Control Blood Pressure in People With Hypertension in Tanzania and Lesotho: A Randomized Clinical Trial.
In 1,268 adults with untreated hypertension in Lesotho and Tanzania, initiating low-dose dual therapy (amlodipine 5 mg + losartan 50 mg) was noninferior to stepped monotherapy for achieving target blood pressure at 12 weeks. Low-dose triple therapy did not significantly outperform monotherapy, and wide confidence intervals suggest uncertainty regarding small effect sizes.
Impact: This pragmatic RCT directly informs first-line antihypertensive strategies in African settings, supporting WHO guidance for early dual therapy while tempering expectations for immediate benefits of triple therapy.
Clinical Implications: Initiating low-dose dual therapy is a viable and noninferior approach for first-line treatment in uncomplicated hypertension in resource-limited settings; triple therapy may be reserved until further evidence clarifies benefits. Implementation should consider medication access and follow-up capacity.
Key Findings
- At 12 weeks, 56% (2-pill) vs 51% (stepped monotherapy) reached BP targets; noninferiority met (aOR 1.18; 95% CI 0.87–1.61).
- Low-dose triple therapy: 57% achieved target vs 49% with stepped monotherapy; not statistically superior (aOR 1.28; 95% CI 0.91–1.79).
- Findings support WHO guidance to start dual therapy and highlight uncertainty (wide CIs) regarding added benefits of triple therapy.
Methodological Strengths
- Multicenter randomized design across two African countries with pragmatic implementation.
- Predefined noninferiority and superiority analyses with intention-to-treat approach and multiple imputation for missing data.
Limitations
- Open-label design and short 12-week follow-up limit detection of long-term differences.
- Wide confidence intervals preclude ruling out clinically meaningful effects of additional pills.
Future Directions: Longer-term, larger-scale trials in diverse LMIC settings should evaluate sustained BP control, adherence, safety, and hard outcomes, and assess cost-effectiveness of dual vs triple therapy initiation.
2. PP2A Attenuates Thoracic Aneurysm and Dissection in Mouse Models of Marfan Syndrome.
In Marfan mouse models, oral activation of PP2A with DT-061 reduced aortic root and ascending aorta expansion, limited medial hypertrophy and elastin breakdown, and decreased metalloproteinase activity. Mechanistically, PP2A activation suppressed mTOR signaling and smooth muscle dedifferentiation, suggesting a disease-modifying therapeutic avenue.
Impact: Identifies PP2A activation as a tractable, small-molecule strategy to counteract mTOR-driven aortopathy in Marfan syndrome, bridging mechanistic insight with translational potential.
Clinical Implications: While preclinical, the data support development of PP2A activators as potential disease-modifying therapies for heritable aortopathies (e.g., Marfan). Clinical translation will require safety profiling, dose-finding, and biomarker-driven trials.
Key Findings
- PP2A activity was reduced and mTOR signaling increased in human and mouse Marfan aortas.
- DT-061 increased PP2A activation and reduced aortic root/ascending aorta expansion, medial hypertrophy, elastin breakdown, and MMP activity.
- Mechanistic analyses indicate suppression of mTOR signaling and smooth muscle cell dedifferentiation as drivers of therapeutic effect.
Methodological Strengths
- Use of two independent Marfan mouse models with convergent results.
- Multimodal assessments (echocardiography, histology, RNA-seq, WB, immunostaining) supporting mechanistic inference.
Limitations
- Preclinical animal models without human efficacy or safety data.
- Potential off-target effects of systemic PP2A activation require careful evaluation.
Future Directions: Advance to IND-enabling studies: pharmacokinetics, toxicology, dose-ranging, and biomarker development; explore synergy or add-on to current Marfan therapies (e.g., ARBs, beta-blockers).
3. Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium: A Cluster Randomized Crossover Trial.
Across 19,768 cardiac surgery patients, an institutional policy restricting intraoperative benzodiazepines did not significantly reduce postoperative delirium within 72 hours (aOR 0.92; P=0.07). No increase in patient-reported intraoperative awareness was detected, suggesting safety but limited efficacy at the policy level.
Impact: Provides definitive large-scale randomized evidence on a common anesthesia practice, informing guideline discussions about benzodiazepine use and highlighting the need for patient-level targeting.
Clinical Implications: Routine institutional restriction of intraoperative benzodiazepines may not meaningfully reduce delirium; consider individualized strategies (e.g., risk stratification, multimodal delirium prevention) while maintaining vigilance for awareness.
Key Findings
- Delirium within 72 hours: 14.0% (restricted) vs 14.9% (liberal); aOR 0.92 (95% CI 0.84–1.01), P=0.07.
- High policy adherence (≈91% restricted vs 93% liberal) and no spontaneous reports of intraoperative awareness.
- Suggests small potential effects; policy-level restriction alone may be insufficient to reduce delirium.
Methodological Strengths
- Large pragmatic cluster randomized crossover design across 20 centers with patient and assessor blinding.
- High adherence to policy assignments and standardized delirium assessments in routine care.
Limitations
- Borderline nonsignificant primary result (P=0.07) and cluster policy-level intervention may dilute patient-level effects.
- Delirium detection relied on routine care tools; potential underdetection or inter-site variability.
Future Directions: Patient-level randomized trials targeting high-risk individuals and multimodal perioperative delirium prevention bundles are warranted; explore dose-response and alternative sedative strategies.